2-formylphenylboronic acid -Drug Synthesis Database

【结构式】

【分子编号】45993

【品名】2-formylphenylboronic acid

【CA登记号】40138-16-7

【分子式】C₇H₇BO₃

【分子量】149.94178

【元素组成】C 56.07% H 4.71% B 7.21% O 32.01%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(III)

3-Iodobenzoic acid (I) was converted to ethyl ester (II) by treatment with DCC and DMAP in ethanol. Subsequent Suzuki coupling of (II) with 2-formylbenzeneboronic acid (III) furnished the biphenyl derivative (IV). Formation of oxime (V) using hydroxylamine hydrochloride, followed by reduction with zinc metal and HOAc, afforded amino ester (VI). Saponification of the ethyl ester (VI) gave amino acid (VII), which was coupled with Fmoc-L-valine (VIII) by means of HBTU to yield amide (IX). This compound was attached to Wang resin using DIPC and DMAP to produce resin (X). Deprotection of the Fmoc group by means of piperidine in DMF then gave the corresponding amino compound (XI). To this were incorporated protected amino acid Fmoc-L-lysine(Z) (XII) followed by a deprotection step with piperidine in DMF, to yield the resin-bound peptide (XIII). (Scheme 29421701a)

参考文献中间体

合成目标

【1】 DeGrado, W.F.; Singh, G.; Reisine, T.; Suich, D.J.; Liapakis, G.; Mousa, S.A.; Template-constrained cyclic peptide analogues of somatostatin: Subtype-selective binding to somatostatin receptors and antiangiogenic activity. Bioorg Med Chem 2000, 8, 9, 2229.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IX),(X)	45998	2'-[[((2S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-methylbutanoyl)amino]methyl][1,1'-biphenyl]-3-carboxylic acid		C₃₄H₃₂N₂O₅	详情	详情
(I)	45991	3-iodobenzoic acid	618-51-9	C₇H₅IO₂	详情	详情
(II)	45992	ethyl 3-iodobenzoate	58313-23-8	C₉H₉IO₂	详情	详情
(III)	45993	2-formylphenylboronic acid	40138-16-7	C₇H₇BO₃	详情	详情
(IV)	45994	ethyl 2'-formyl[1,1'-biphenyl]-3-carboxylate		C₁₆H₁₄O₃	详情	详情
(V)	45995	ethyl 2'-[(hydroxyimino)methyl][1,1'-biphenyl]-3-carboxylate		C₁₆H₁₅NO₃	详情	详情
(VI)	45996	ethyl 2'-(aminomethyl)[1,1'-biphenyl]-3-carboxylate		C₁₆H₁₇NO₂	详情	详情
(VII)	45997	2'-(aminomethyl)[1,1'-biphenyl]-3-carboxylic acid		C₁₄H₁₃NO₂	详情	详情
(VIII)	19932	(2S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-methylbutyric acid		C₂₀H₂₁NO₄	详情	详情
(XI)	45999	2'-([[(2S)-2-amino-3-methylbutanoyl]amino]methyl)[1,1'-biphenyl]-3-carboxylic acid		C₁₉H₂₂N₂O₃	详情	详情
(XII)	46001	N-alpha-Fmoc--N-epsilon-Z-L-lysine; Fmoc-Nepsilon-Z-L-lysine; N-epsilon-Z-N-alpha-Fmoc-L-lysine; (2S)-6-[[(benzyloxy)carbonyl]amino]-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]hexanoic acid	86060-82-4	C₂₉H₃₀N₂O₆	详情	详情
(XIII)	46000	2'-[(4S,7S)-7-amino-4-isopropyl-3,6,13-trioxo-15-phenyl-14-oxa-2,5,12-triazapentadec-1-yl][1,1'-biphenyl]-3-carboxylic acid		C₃₃H₄₀N₄O₆	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

Alkylation of 2,4-di-tert-butyl-6-iodophenol (I) with bromopropane by means of NaH (1) or CsF (2) provides the corresponding propyl ether (II). Subsequent Suzuki coupling of aryl iodide (II) with 2-formylbenzeneboronic acid (III) leads to the biphenyl aldehyde (IV). This is then condensed with phosphonate (V) producing the dienoate ester (VI). Finally, the ethyl ester group of (VI) is hydrolyzed with LiOH to the target carboxylic acid (1,2).

参考文献中间体

合成目标

【1】 Chen, J-H.; Michellys, P-Y.; Ardecky, R.J.; Tyhonas, J.S.; Leibowitz, M.D.; Liu, S.; Rungta, D.; D'Arrigo, J.; Mais, D.E.; Miller, A.; Grese, T.A.; Mapes, C.M.; Thompson, A.W.; Boehm, M.F.; Ogilvie, K.M.; Karanewsky, D.S.; RXR modulators. Design and synthesis of new RXR-selective phenyl- and pyridine-locked dienoic acids for the treatment of type 2 diabetes. 225th ACS Natl Meet (March 23 2003, New Orleans) 2003, Abst MEDI 262.
【2】 Jones, T.K.; Ardecky, R.J.; Boehm, M.F.; Hamann, L.G.; Thompson, A.J.; Michellys, P.-Y.; Tyhonas, J.S.; Faulkner, A.L.; Mapes, C.M.; Chen, J.-H. (Ligand Pharmaceuticals, Inc.); RXR modulators with improved pharmacologic profile. EP 1216221; WO 0119770 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	63974	2,4-di(tert-butyl)-6-iodophenol		C₁₄H₂₁IO	详情	详情
(II)	63975	1,5-di(tert-butyl)-3-iodo-2-propoxybenzene; 2,4-di(tert-butyl)-6-iodophenyl propyl ether		C₁₇H₂₇IO	详情	详情
(III)	45993	2-formylphenylboronic acid	40138-16-7	C₇H₇BO₃	详情	详情
(IV)	63976	3',5'-di(tert-butyl)-2'-propoxy[1,1'-biphenyl]-2-carbaldehyde		C₂₄H₃₂O₂	详情	详情
(V)	44704	ethyl (E)-4-(diethoxyphosphoryl)-3-methyl-2-butenoate	41891-54-7	C₁₁H₂₁O₅P	详情	详情
(VI)	63977	ethyl (2E,4E)-5-[3',5'-di(tert-butyl)-2'-propoxy[1,1'-biphenyl]-2-yl]-3-methyl-2,4-pentadienoate		C₃₁H₄₂O₃	详情	详情

Extended Information